My research interests relate to mitochondrial and cellular bioenergetics, including studies of oxidative phosphorylation in isolated mitochondria, mitochondrial dysfunction in toxic, hypoxic and reperfusion injury to hepatocytes, cardiac myocytes and organs stored for transplantation surgery, and control of metabolism. Our in vitro and in vivo studies of living cells and tissues have shown that mitochondrial calcium uptake, iron translocation from lysosomes to mitochondria, and oxidative stress promote the mitochondrial permeability transition (MPT). The MPT initially induces lysosomal degradation of mitochondria by autophagy, a selective process called mitophagy. However, excess MPT induction induces both necrotic cell death from ATP depletion and apoptosis due to cytochrome c release after mitochondrial swelling. Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia/hypoxia, alcoholic liver disease and aerobic glycolysis in cancer cells (Warburg effect). My lab is examining and supporting the novel hypothesis that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane accounts for global mitochondrial suppression consistent with a role for VDAC as a dynamic regulator, or governator, of global mitochondrial function both in health and disease. For these projects, my laboratory extensively applies new techniques of quantitative laser scanning confocal and intravital multiphoton microscopy for physiological analysis of single cells and living tissues.